Chapter 5: The Organelles – Structure and Function in Eukaryotic Cells

Chapter 5: The Organelles

Introduction to Eukaryotic Cells

Eukaryotic cells are characterized by the presence of a true nucleus and various membrane-bound organelles, distinguishing them from prokaryotic cells. These organelles compartmentalize cellular functions, allowing for greater complexity and specialization.

• DNA is enclosed within a nuclear envelope.

• Organelles are specialized sub-compartments with distinct functions.

• The cytoplasm is the region between the plasma membrane and the nucleus.

• Eukaryotic cells are generally larger than prokaryotic cells.

Definition and Types of Organelles

An organelle is a discrete structure within a eukaryotic cell, specialized for a particular function. Organelles can be membrane-bound or non-membranous.

• Membranous organelles: Nucleus, endoplasmic reticulum (ER), Golgi apparatus, mitochondria, lysosomes, peroxisomes, vacuoles, and vesicles.

• Non-membranous structures: Ribosomes, centrioles, microtubules, actin filaments, intermediate filaments.

The Nucleus

Structure and Function

The nucleus is the control center of the cell, containing most of the cell’s genetic material. It is typically a single, prominent structure per cell, except in specialized cells such as erythrocytes and platelets, which lack a nucleus.

• Enclosed by a double-membrane nuclear envelope.

• Contains nuclear pores for regulated molecular traffic.

• Contains the nucleolus, the site of ribosomal RNA (rRNA) synthesis.

Nuclear Envelope and Lamina

The nuclear envelope consists of two lipid bilayer membranes (inner and outer), with the outer membrane continuous with the endoplasmic reticulum. The nuclear lamina, a protein matrix, supports nuclear shape and organizes chromatin.

Nuclear Pores

Nuclear pores are large protein complexes that regulate the entry and exit of molecules between the nucleus and cytoplasm. They allow passive diffusion of small molecules and ions, and active, regulated transport of macromolecules such as proteins and RNAs via nuclear localization signals (NLS).

Functions of the Nucleus

• Separates and protects DNA from cytoplasmic enzymes and chemicals.

• Contains enzymes and proteins for DNA metabolism (packaging, repair, replication, transcription).

Nuclear Compartments

• Nuclear envelope

• Nuclear cytoskeleton (lamina)

• Nucleolus

• Chromosome territories

• Interchromatin compartment

• Speckles (interchromatin granule clusters)

• Nuclear bodies (Cajal and PML bodies)

The Nucleolus

The nucleolus is a prominent, basophilic structure within the nucleus, visible by light microscopy. It is the site of rRNA synthesis and ribosome assembly, and is formed by regions of several chromosomes (nucleolar organizing regions, NORs).

• Composed of fibrillar centers (FC), fibrillar material (F), and granular material (G).

• Disappears during mitosis.

Nucleolar Organizing Regions (NORs)

• Located on chromosomes 13, 14, 15, 21, and 22.

• Encode 18S, 28S, and 5.8S rRNAs.

• Essential for rRNA transcription and nucleolus assembly.

Nuclear Lamina

The nuclear lamina is a meshwork of intermediate filament proteins (lamins) that provides structural support and organizes chromatin within the nucleus.

Nuclear Envelope

The nuclear envelope forms a double-membrane barrier around the nucleus. The outer membrane is continuous with the endoplasmic reticulum. The envelope contains nuclear pores and breaks down during mitosis.

Nuclear Pores (Detailed)

• External diameter: ~120 nm; channel diameter: ~25 nm.

• Allow passive passage of small polar molecules and ions.

• Active, selective passage of macromolecules (proteins, RNAs) via NLS.

Ribosomes

Structure and Function

Ribosomes are complexes of rRNA and protein, responsible for protein synthesis. They exist as free ribosomes in the cytosol or bound to the ER or nuclear envelope.

• Free ribosomes synthesize cytosolic proteins.

• Bound ribosomes synthesize proteins for secretion or membrane insertion.

The Endomembrane System

Components and Functions

The endomembrane system regulates protein traffic and performs metabolic functions. It includes the nuclear envelope, ER, Golgi apparatus, lysosomes, vacuoles, and plasma membrane. These components are interconnected directly or via vesicular transport.

The Endoplasmic Reticulum (ER)

Structure and Types

The ER is a network of membranes continuous with the nuclear envelope. It is divided into smooth ER (SER) and rough ER (RER).

• Smooth ER: Lacks ribosomes; involved in lipid synthesis, carbohydrate metabolism, detoxification, and calcium storage (sarcoplasmic reticulum in muscle).

• Rough ER: Studded with ribosomes; site of synthesis of secretory and membrane proteins.

Smooth ER Functions

• Synthesizes lipids (triglycerides, phospholipids, sterols).

• Metabolizes carbohydrates.

• Detoxifies poisons.

• Stores calcium (especially in muscle cells).

• Phospholipid synthesis occurs on the cytosolic side; "scramblases" transfer lipids across the bilayer.

Phospholipid Distribution and Golgi Function

• Phospholipid distribution is asymmetric in membrane bilayers.

• "Flippases" in the Golgi selectively move phosphatidylserine (PS) and phosphatidylethanolamine (PE) to the cytosolic monolayer.

• Phosphatidylcholine (PC) and sphingomyelin are concentrated on the non-cytosolic monolayer.

Rough ER Functions

• Has bound ribosomes that synthesize glycoproteins.

• Distributes transport vesicles containing proteins.

• Acts as a membrane factory for the cell.

ER Stress and Protein Quality Control

The RER ensures proper folding of newly synthesized proteins via chaperones. Misfolded proteins are exported, ubiquitinated, and degraded by proteasomes. Accumulation of misfolded proteins triggers ER stress, which can be caused by mutations, viral infection, increased secretory demand, ischemia, or aging.

The Unfolded Protein Response (UPR)

The UPR is a cellular stress response to manage misfolded proteins in the ER. If stress is manageable, the cell increases chaperone production, enhances proteasomal degradation, and reduces overall protein translation. If unresolved, apoptosis is triggered. ER stress is implicated in neurodegenerative diseases, type 2 diabetes, fatty liver disease, and ischemia-reperfusion injury.

The Golgi Apparatus

Structure and Function

The Golgi apparatus consists of flattened sacs (cisternae) with a "cis" face (receiving side) and a "trans" face (shipping side). It modifies, sorts, and packages proteins and lipids from the ER for delivery to their destinations.

• Modifies ER products (e.g., glycosylation).

• Manufactures certain macromolecules.

• Sorts and packages materials into transport vesicles.

Protein Sorting and Trafficking in the Golgi

• Lysosomal enzymes are labeled early in the cis Golgi network.

• In the trans Golgi, glycoproteins combine with receptors for targeting.

• Membranes are recycled during vesicular transport.

Mitochondria

Structure and Function

Mitochondria are the sites of cellular respiration and ATP production. They are not part of the endomembrane system and have a double membrane with inner folds called cristae, increasing surface area for ATP synthesis.

• Inner membrane creates intermembrane space and mitochondrial matrix.

• Contain their own DNA and ribosomes.

• Proteins are encoded by both mitochondrial and nuclear genomes.

• Inherited maternally.

Functions of Mitochondria

• Produce ATP via oxidative phosphorylation.

• Oxidative catabolism of glucose and fatty acids (citric acid cycle).

• More abundant in metabolically active cells (e.g., muscle).

Genetic System of Mitochondria

• Mitochondrial matrix contains mtDNA, mRNA, tRNA, and rRNA.

• Human mitochondrial genome encodes 13 proteins for electron transport and oxidative phosphorylation.

• Germline mutations are maternally inherited.

Endosymbiotic Hypothesis

The endosymbiotic hypothesis proposes that mitochondria (and chloroplasts in plants) originated from aerobic bacteria engulfed by ancestral eukaryotic cells, supported by phylogenetic evidence.

Lysosomes

Structure and Function

Lysosomes are membrane-bound sacs containing hydrolytic enzymes for digesting macromolecules. Enzymes and membranes are synthesized in the RER and Golgi. Lysosomes degrade proteins, fats, polysaccharides, and nucleic acids.

Pathways for Material Entry

• Phagocytosis: Engulfment of large particles (e.g., by macrophages).

• Autophagy: Digestion of cellular components.

• Receptor-mediated endocytosis: Uptake of specific extracellular materials.

Lysosomal Properties

• ATP-driven proton pumps maintain acidic pH (~5).

• Glycoprotein coat protects against self-digestion.

• Transporter channels export breakdown products.

Lysosomal Enzymes

• Hydrogen ion ATPases actively transport protons into the lysosome.

• Acid hydrolases function optimally at low pH.

• Enzymes are inactive in the cytosol (pH 7.2), preventing cellular damage if released.

Lysosomal Storage Diseases

These are genetic disorders caused by mutations in genes encoding lysosomal enzymes, leading to substrate accumulation and cellular damage. Neurons are particularly susceptible. Most are autosomal recessive and vary in onset and severity.

Disease	Defective Enzyme	Accumulated Substrate
Tay-Sachs disease	Hexosaminidase A	GM2 gangliosides
Gaucher's disease	Glucocerebrosidase	Glucocerebrosides
Mucopolysaccharidoses	Various hydrolases	Glycosaminoglycans

Peroxisomes

Structure and Function

Peroxisomes are single-membrane-bound organelles containing oxidases and catalase. They produce and degrade hydrogen peroxide, oxidize very long-chain and branched-chain fatty acids, and regulate cellular ROS levels.

• CATALASE/oxidase reaction: $2H_2O_2 \rightarrow 2H_2O + O_2$

• Divide by fission to form daughter peroxisomes.

Peroxisome Deficiencies

• Zellweger syndrome: Deficiency in peroxisome biogenesis; accumulation of VLCFAs and toxic substances.

• Adrenoleukodystrophy (X-linked): ABCD1 deficiency; impaired VLCFA breakdown, CNS/PNS demyelination, adrenocortical insufficiency.

Other Organelles

Melanosomes

• Found in melanocytes (skin, hair follicles, eyes).

• Produce melanin pigment.

Centrioles

• Paired, barrel-shaped organelles in animal cells and some plants.

• Form the basis of centrosomes, cilia, and flagella.

• Act as microtubule-organizing centers (MTOCs).